Collectively Encoded Rydberg Qubit.

We demonstrate a collectively encoded qubit based on a single Rydberg excitation stored in an ensemble of N entangled atoms. Qubit rotations are performed by applying microwave fields that drive excitations between Rydberg states. Coherent readout is performed by mapping the excitation into a single photon. Ramsey interferometry is used to probe the coherence of the qubit, as well as to test the robustness to external perturbations. We show that qubit coherence is preserved even as we lose atoms from the polariton mode, preserving Ramsey fringe visibility. We show that dephasing due to electric field noise scales as the fourth power of field amplitude. These results show that robust quantum information processing can be achieved via collective encoding using Rydberg polaritons, and hence this system could provide an attractive alternative coding strategy for quantum computation and networking.

Single-photon stored-light Ramsey interferometry using Rydberg polaritons.

We demonstrate a single-photon stored-light interferometer, where a photon is stored in a laser-cooled atomic ensemble in the form of a Rydberg polariton with a spatial extent of 10×1×1µm3. The photon is subject to a Ramsey sequence, i.e., "split" into a superposition of two paths. After a delay of up to 450 ns, the two paths are recombined to give an output dependent on their relative phase. The superposition time of 450 ns is equivalent to a free-space propagation distance of 135 m. We show that the interferometer fringes are sensitive to external fields and suggest that stored-light interferometry could be useful for localized sensing applications.

Randomized controlled trial of fibrin sealant to reduce postoperative drainage following elective lymph node dissection.

BACKGROUND: Excessive postoperative drainage following groin and axillary lymphadenectomy may be associated with a prolonged hospital stay and an increased complication rate. The use of fibrin sealant before wound closure may reduce postoperative wound drainage. METHODS: Consecutive patients undergoing elective groin or axillary lymphadenectomy were randomized to standard wound closure or to having fibrin sealant sprayed on to the wound bed before closure. Postoperative wound drainage, duration of drainage and complications were recorded, as were locoregional recurrence, distant metastasis and mortality. RESULTS: A total of 74 patients requiring 38 groin and 36 axillary dissections were randomized. The median postoperative wound drainage volume for the groin dissection cohort was 762 (range 25-3255) ml in the control group and 892 (265-2895) ml in the treatment group (P = 0·704). Drainage volumes in the axillary cohort were 590 (230-9605) and 565 (30-1835) ml in the control and treatment groups respectively (P = 0·217). There was no difference in the duration of drainage or postoperative complication rate between the treatment groups in both the axillary and groin cohorts. Local recurrence, distant metastasis and mortality rates did not differ between the treatment groups. CONCLUSION: There was no advantage in using fibrin sealant during elective lymphadenectomy in terms of reducing drainage output or postoperative complication rate.

Multi-targeted directed ligands for Alzheimer's disease: design of novel lead coumarin conjugates.

Alzheimer's Disease (AD) is a neurodegenerative disease characterized by central nervous system insults with progressive cognitive (memory, attention) and non-cognitive (anxiety, depression) impairments. Pathophysiological events affect predominantly cholinergic neuronal loss and dysfunctions of the dopaminergic system. The aim of the current study was to design multi-targeted directed lead structures based on the coumarin scaffold with inhibitory properties at two key enzymes in disease relevant systems, i.e. acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). Conventional and microwave synthetic methods were utilized to synthesize coumarin scaffold-based novel morpholino, piperidino, thiophene and erucic acid conjugates. Biological assays indicated that the coumarin-morpholine ether conjugate BPR 10 was the most potent hMAO-B inhibitor. The coumarin-piperidine conjugates BPR 13 and BPR 12 were the most potent inhibitors of eeAChE at 100 µM and 1 µM, respectively. Molecular modelling studies were conducted with Accelrys® Discovery Studio® V3.1.1 utilising the published hMAO-B (2V61) and hAChE (4EY7) crystal structures. Compound BPR 10 occupies both the entrance and substrate cavities of the active site of MAO-B. BPR 13 resides in both the peripheral anionic site (PAS) and the catalytic anionic site (CAS) of hAChE. This study demonstrated that the coumarin scaffold serves as a promising pharmacophore for MTDLs design.

Synthesis and biological activity of D3-trishomocubyl-4-amines.

The D3-trishomocubyl system was prepared from tertiary pentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecan-8-ols 5 in one step by using a modified Ritter reaction yielding only one of the possible two geometrical isomers of 4-amino-3-alkyl (or aryl)-D3-trishomocubane (8). Promising antagonism of reserpine-induced catalepsy was exhibited by these compounds which compared favorable with that of amantadine. Weak to mild anticholinergic properties were observed during the reduction of oxotremorine induced tremor and salivation procedure. Acute toxicities similar to that of amantadine were observed for some of these compounds. D3-Trishomocubyl-4-amines appeared as a promising new class of anti-Parkinson agents.

Technetium-99m-HMPAO, technetium-99m-ECD and iodine-123-IMP cerebral blood flow measurements with pharmacological interventions in primates.

UNLABELLED: Technetium-99m-bicisate ethyl cysteinate dimer (ECD) presents a different pattern from cerebral blood flow (CBF) in the subacute phase of cerebral infarction, as measured by PET, perhaps due to lack of oxygen and enzyme activity; this pattern is contrary to that of hexamethyl-propyleneamine oxime (HMPAO) but similar to that of N-isopropyl-[123I]beta-iodoamphetamine ([123I]IMP). This study explores possible CBF differences among HMPAO, ECD and IMP, with various relevant drug interventions. METHODS: Anesthetized adult baboons were used in these SPECT studies. Four studies (n = 6 baboons for each study), one control study and three intervention studies involving intravenous acetazolamide, nimodipine infusion and intramuscular sumatriptan, were followed with 99mTc-HMPAO, 99mTc-ECD and [123I]IMP. The split-dose method was used as follows. For each tracer, intervention data from the second SPECT (SPECT-2) after the second tracer injection (444 MBq) reflected a change in CBF with respect to the baseline SPECT (SPECT-1) data from the initial injection (222 MBq). These changes as a ratio, R (R = SPECT-2/SPECT-1), for each study, and the R values for each tracer were compared to R values from the corresponding control studies, yielding a quantitative estimate of drug effects. RESULTS: There were no significant differences (p > 0.05) between HMPAO and ECD for the control, acetazolamide and sumatriptan studies, but there was indeed a difference between the two for the nimodipine study, indicating a nimodipine-dependent underestimation of CBF with ECD (and also with IMP), with respect to HMPAO. A further significant difference was that larger CBF increases were observed with acetazolamide, as measured with [123I]IMP. CONCLUSION: This is a crucial observation for the clinical interpretation of CBF SPECT data and should direct the choice of tracer for a specific examination.

Characterization of the enzymatic activity for biphasic competition by guanoxabenz (1-(2,6-dichlorobenzylidene-amino)-3-hydroxyguanidine) at alpha2-adrenoceptors. I. Description of an enzymatic activity in spleen membranes.

The mechanism for formation of high-affinity binding of 1-(2,6-dichlorobenzylidene-amino)-3-hydroxyguanidine (guanoxabenz) to alpha2-adrenoceptors was studied in particulate fractions from the rat spleen. The proportion of apparent high versus low-affinity alpha2-adrenoceptor binding sites increased with increasing incubation time and was also augmented by Mg2+ ions. The formation of high-affinity guanoxabenz binding seemed to be inhibited by a series of N-hydroxyguanidine analogs to guanoxabenz, as well as by a series of metabolic inhibitors that included allopurinol, 1-chloro-2,4-dinitrobenzene, 5,5'-dithiobis-(2-nitrobenzoic acid), cibacron blue, phenyl-p-benzoquinone, didox, and trimidox. The formation of guanoxabenz high-affinity binding was also inhibited in a time- and concentration-dependent fashion by preincubating the membranes with the LW03 N-hydroxyguanidine analogue of guanoxabenz. Moreover, when the spleen membranes were extensively washed for 30 min with buffers at 25 degrees, the guanoxabenz high-affinity binding disappeared. However, when these washed membranes were supplemented with xanthine, the apparent affinity of guanoxabenz increased four to five-fold. Taken together, all data were compatible with the theory that the formation of high-affinity binding was dependent on the generation of a guanoxabenz metabolite that showed an approximate 100-fold greater affinity for the alpha2-adrenoceptors than guanoxabenz itself. Because the most potent blocker of the formation of high-affinity binding was allopurinol (apart from some N-hydroxyguanidine analogs to guanoxabenz) and since the activity could be restored with xanthine, a likely candidate responsible for the metabolic activation is xanthine oxidase.

Long-term treatment with the tetrahydropyridine analog (HPTP) of haloperidol influences dopamine ligand binding in baboon brain. An [123I]iodobenzamide (IBZM) SPECT study.

Haloperidol (HP) and its tetrahydropyridine dehydration product 4-(4-chlorophenyl)-[4-(fluorophenyl)-4-oxobutyl]-1,2,3,6-tetrahydropyrid ine (HPTP) are both metabolized in vivo to several pyridinium metabolites with potential neurotoxic properties similar to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+), a metabolite of the parkinsonian-inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The effect of long-term HPTP treatment on the central nervous system of baboons (Papio ursinus) was studied using [123I]iodobenzamide (IBZM) and single photon emission computed tomography (SPECT) at 1-14 weeks after termination of HPTP treatment. Striatal dopamine receptor binding was measured semiquantitatively by calculating the IBZM count rate ratios of the basal ganglia to frontal cortex and basal ganglia to cerebellum. Relative striatal perfusion was assessed by similar 99mTc-HMPAO (hexamethylpropylene amine oxime) ratios. Time activity curves of IBZM from the brain structures suggest that HPTP treatment results in a marked reduction in central dopamine ligand binding, and in particular D2-like receptor binding. Increased washout of the ligand from all the brain structures investigated was seen in the HPTP-treated animals, also consistent with reduced binding. Cerebral blood flow in the control and HPTP-treated groups was similar, indicating that this did not account for the reduced dopamine receptor binding of the IBZM ligand. These data suggest that treatment with HPTP induces significant effects on dopamine receptor binding that may contribute to some of the neurological disorders observed in humans undergoing chronic HP treatment.

A model for agonists acting directly as well as indirectly.

A theoretical model is presented to describe the receptor interaction of a drug which possesses indirect as well as direct pharmacological action. Sets of theoretical log concentration-effect curves predicted by this model are presented. The model predicts that the shape of the log concentration-effect curves may be sigmoid (S-shaped), biphasic (bell-shaped) or composed of a combination of two sigmoid curves, joined together by a plateau. The theoretical predictions are comparable with the results obtained from an experimental study.

A comparative cerebral blood flow study in a baboon model with acetazolamide provocation: 99mTc-HMPAO vs 123I(IMP).

Pharmacological interactions are important when nuclear medical procedures are applied to patients under drug therapy, or drug provocation. This study compares in baboon models (regional) cerebral blood flow [(r)CBF] results from 99mTc-HMPAO and 123I-iodoamphetamine [123I(IMP)] each with and without acetazolamide, the latter a suggested drug for testing cerebrovascular reserve. Expected differences in cerebral uptake were observed between the two radio-tracers without acetazolamide. The increase in tracer uptake resulting from acetazolamide is significantly enhanced for 123I(IMP), which could have diagnostic implications.

The effects of herbal oxytocics on the isolated "stripped" myometrium model.

Decoctions of Agapanthus africanus and Clivia miniata are used as oxytocic agents in South African traditional herbal medicine. Aqueous extracts of A. africanus and C. miniata leaves have been shown to possess similar uterotonic activities in the isolated whole uterus preparation. The uterus however, comprises a myometrial and an endometrial layer and the activity of both oxytocin and the prostaglandins differs in these layers. The aim of this study was to determine the uterotonic activity of the herbal remedies in an endometrium-free preparation (i.e. "stripped" myometrium) and, if active, whether this effect could be related to prostaglandin synthesis or to interaction with specific receptors. The effects of the herbal extracts were tested on the isolated "stripped" rat myometrium preparation. Both herbal extracts caused a direct contractile response by the isolated tissue. Pretreatment of the myometrium with either plant extract augmented the initial response to acetylcholine. Preincubation with atropine inhibited the response to cumulative dosage of Agapanthus extract but had no effect on the response to Clivia. Indomethacin administration did not affect the response of the myometrium to cumulative dosage of acetylcholine, oxytocin or Clivia extract but inhibited the response to Agapanthus extract. These results clearly indicate that the Agapanthus and Clivia herbal extracts exhibited uterotonic activity in this model. The study illustrates that the "stripped" myometrium model has successfully differentiated between the mechanisms of action of two herbal oxytocics compared to the whole uterus preparation where their uterotonic activity was thought to be similar.

Dopamine receptor binding of 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)- 4-oxobutyl]-1,2,3,6-tetrahydropyridine (HPTP), an intermediate metabolite of haloperidol.

The neuroleptic agent haloperidol (HP) is biotransformed to metabolites such as 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3,6- tetrahydropyridine (HPTP) and 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]pyridinium (HPP+). In this study, radioligand binding studies were performed using [3H]SCH23390 as a dopamine D1 receptor ligand and [3H]spiperone as a D2 ligand. Ki values for D1 receptors were 35.8 microM and 54.9 microM for HP and HPTP, respectively. Corresponding values for D2 receptors were 39.1 nM and 329.8 nM. These results indicate similar low affinities in the micromolar range for both HP and HPTP at the dopamine D1 receptor, a much higher affinity of both HP and HPTP for the D2 receptor than for the D1 receptor, and that HPTP binds to D2 receptors with a 9-fold lower affinity than HP. The data are consistent with observations in mice that HPTP is a much less potent acute neuroleptic agent than HP.

In vivo measurements of the cerebral perfusion and cardiovascular effects of the novel guanidine ME10092 in the non-human primate, Papio ursinus.

The novel guanidines N-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine (ME 10092) and N-(3,4-dimethoxy-2-chlorobenzylideneamino)-N1-hydroxyguanidine (PR5) were recently reported to exhibit promising cardioprotective activities in myocardial ischaemia and reperfusion in rats. The current study investigated for the first time pharmacological effects of ME10092 in the primate, viz. the Cape baboon Papio ursinus. The effects of ME10092 (1 and 2 mg/kg doses) on the cerebral blood flow, heart rates and the systolic and diastolic blood pressure were investigated after intravenous injection to the baboon under anaesthesia. The cerebral perfusion effects of ME10092 were assessed using Single Photon Emission Computed Tomography according to the split-dose approach and 99mTc-hexamethyl-propylene amine oxime as brain perfusion tracer. The observation that the recovery times from the anaesthesia were unacceptably prolonged excluded doses beyond 2 mg/kg. The data indicate that no cerebral perfusion changes were induced at both the 1 and 2 mg/kg doses of ME10092. Both these doses of ME10092 showed blood pressure and heart rate effects, with the latter being more significant. Decreases in heart rate were seen directly after ME10092 administration reaching levels of about 20% for the 2 mg/kg dose and about 15% for the 1 mg/kg dose at around 6 min post drug administration. A transient decrease in both systolic and diastolic blood pressure was observed for the higher dose. The blood pressure data further suggest an attenuation of the anaesthesia induced increase in pressure usually present in non-intervention studies. ME10092 clearly exhibits mycocardial effects in the non-human primate, similar to the effects previously observed in the ischaemia-reperfusion rat model, where ME10092 showed strong protection.

High-resolution solid-state carbon-13 nuclear magnetic resonance spectra of mofebutazone, phenylbutazone, and oxyphenbutazone in relation to X-ray crystallographic data.

The solid-state 13C NMR spectra of mofebutazone, phenylbutazone, and oxyphenbutazone monohydrate and anhydrate are presented. The crystal structures of these pyrazolidinedione derivatives, obtained by single-crystal X-ray analysis, were previously reported, revealing distinct differences in crystal structure. In this report, the chemical shift values observed for the solid-state 13C spectra are related to the chemical environment of the various carbon atoms and compared with the crystallographic data. Results indicate that solid-state NMR spectroscopy is potentially useful in the study of drugs in the solid state.

Massive plexiform neurofibroma of the sympathetic trunk.

A case report of a massive plexiform neurofibroma of the sympathetic trunk is reported. Symptoms included dysphagia, shortness of breath and paraesthesia of the right hand. The nerve of origin and extent of the tumour were unusual. The tumour mass partially filled the right hemithorax, surrounded the right brachial plexus, extended to the base of skull and invaded the cervical vertebrae threatening to compromise the spinal cord. Surgical resection required combined cardiothoracic, neurosurgical and plastic and reconstructive surgical teams. Early outcome following surgery was excellent. This case illustrates the need for a combined surgical approach for such a lesion and we believe it is the first reported case of plexiform neurofibroma of the sympathetic trunk.

Drug effects on cerebral blood flow in the baboon model--acetazolamide and nimodipine.

The sensitivity of the baboon model under anaesthesia for single photon emission computed tomography (SPECT) of the brain with 99mTc-HMPAO, as recently developed by us to study cerebral blood flow patterns, was investigated using drugs that are known to increase cerebral blood flow, e.g. acetazolamide, the carbonic anhydrase inhibitor and nimodipine, the calcium channel blocker. Increases in cerebral blood flow for both acetazolamide and nimodipine were observed that correspond well with other studies. Statistically significant regional specificity was noted for acetazolamide and nimodipine. Interestingly a combination of these drugs did not enhance cerebral blood flow but rather decreased it in comparison with the individual drug responses. The results were correlated with arterial blood pressure, heart rate, pCO2 and pO2. A blood pressure decrease was noted for both drugs, while acetazolamide had a marked influence on pO2. The results indicate that the baboon model is sensitive for evaluation of drug effects on cerebral blood flow.

Dose response from pharmacological interventions for CBF changes in a baboon model using 99Tcm-HMPAO and SPECT.

This study assesses the sensitivity of the baboon model under anaesthesia to determine by single photon emission computed tomography (SPECT) and 99Tcm-hexamethylpropyleneamine oxime (HMPAO) dose responses from drugs (acetazolamide) with known regional cerebral blood flow (rCBF) effects on humans. Three dosages of acetazolamide were chosen: 250, 500 and 750 mg. The effects of these were studied by conventional SPECT 5 min after intravenous (i.v.) administration and compared to previous studies of rCBF with the baboons under anaesthesia only. An additional study concerned the effect of 500 mg acetazolamide at 15 min after administration. Haemodynamic parameters and blood gases were also monitored. No statistically significant regional effects were noted (P > 0.05). The largest increase in CBF (39%) was observed from 500 mg acetazolamide after 5 min. This was statistically significantly different from control values only at a 10% level of confidence; then followed a 27% increase above control values after 750 mg (5 min). At 15 min 500 mg yielded values lower by 10% than the high dose. No effects were observed from 250 mg acetazolamide; only pO2 showed changes which largely confirm the CBF findings. The model did not give significant results at a 5% level of confidence but large fluctuations were observed, also in the haemodynamic and blood gas values. At a 10% level a significant dose response was confirmed for acetazolamide.

Discrimination between the functional and biochemical effects of two herbal oxytocics on the rat myometrium.

This study on the rat myometrium is the first report where the effects of herbal extracts used as oxytocics in traditional medicine have been systematically analysed in the same preparation at the level of functional (contractile) and biochemical (second messenger generation) responses. Extracts of Agapanthus africanus and Clivia miniata (used in South African traditional medicine) were compared with other uterotonic agents with regard to their ability to stimulate phosphoinositide metabolism in the rat myometrium and cause accumulation of [3H]inositol phosphates. The maximal contractile response of the isolated rat myometrium in response to stimulation by the herbal extracts and agonists was compared with the maximal contractile response to cumulative addition of acetylcholine. The rank order of intensity of stimulation of [3H]inositol phosphate generation was: oxytocin > Agapanthus > prostaglandin F2alpha(PGF2alpha) > serotonin > acetylcholine > Clivia > ergometrine. This differed from the rank order of maximum contractile response: oxytocin > acetylcholine > PGF2alpha > serotonin approximately Clivia > Agapanthus > ergometrine. Activity was also identified in chemical fractions of the plants and components common to both plants have been identified in the isolated active fractions. These results have identified that the uterotonic activity of Agapanthus is linked to increased turnover of phosphoinositides as a signal transduction mechanism, whereas this appears to play a less significant role in the uterotonic activity of Clivia. This study illustrates the benefits of using the measurement of stimulation of phosphoinositide metabolism as a bioassay in phytomedical research.

A prospective, randomized, double-blind trial of the use of fibrin sealant for face lifts.

Fibrin sealant imitates the final phase of the blood coagulation process. Fibrinogen is converted into fibrin on a tissue surface by the action of thrombin, which is then cross-linked by factor XIIIa, creating a mechanically stable fibrin network. This fibrin network is thought to reduce the amount of postoperative bleeding by sealing capillary vessels and allowing raw operative surfaces to adhere. The authors conducted a prospective, double-blind, randomized, controlled trial on the use of fibrin sealant in 20 consecutive patients undergoing bilateral face lifts by the same surgeon. Each patient was randomized for the use of fibrin sealant on either the right or the left side with the contralateral side acting as the control. Total drainage was recorded on each side for 24 hours before drains were removed. The age range of the patients in the trial (all of whom were women) was 44 to 70 years (mean, 55). The side treated with fibrin glue had a median drainage of 10 ml and the control side 30 ml. The Wilcoxon signed rank test shows a significant difference in drainage between sides (p = 0.002). The reduction in postoperative drainage could also reduce pain and bruising, increasing patient satisfaction with this procedure. The need for drains may also be obviated.

South African traditional herbal medicines used during pregnancy and childbirth.

Many black South African women use traditional herbal remedies as antenatal medications or to induce or augment labour. Very little is known about the pharmacology and potential toxicity of the plants used in these herbal remedies. The ethnic background and traditional usage of these remedies was researched and a literature survey revealed that 57 different plants were used in herbal remedies during pregnancy and childbirth. Several of these plants are poisonous and details of their toxicity are given.